Urease inhibition and anti-leishmanial assay of substituted benzoylguanidines and their copper(II) complexes

A series of N,N',N'-trisubstituted guanidines (1-6) and their copper(II) complexes, [κ(2)(O,N)-C(6)H(5)CONHC(NHC(6)H(4)Cl)NR](2)Cu(ii) (R = iso-propyl (1a), n-butyl (2a), sec-butyl (3a), tert-butyl (4a), benzyl (5a), and para-tolyl (6a)) were synthesized and characterized using elemental analysis, FTIR and NMR spectroscopy. DFT studies were used to assess the location of the protons in the free ligands. However, calculations have shown that, in all cases, hydrogen bonding from either N-H group gives conformations that are very similar in energy. Single crystal XRD studies were used to characterize ligands 1 and 4 and the related complexes 1a and 4a. The structures reveal that these complexes are mononuclear in the solid state and that copper adopts a regular square planar geometry. In both metallic species, the N, N', N'-trisubstituted guanidine ligands chelate the Cu(II) atom using the oxygen and one nitrogen. The synthesized compounds were investigated for urease inhibition using thiourea as a standard drug. Most complexes exhibit a better activity than the respective guanidines and compound 1a was found to be the most active with IC(50) = 9.83 ± 0.07 μM (the IC(50) for thiourea is 21.0 ± 0.1 μM). The species were also screened for their anti-leishmanial activity. However, all of the compounds were devoid of any significant activity.     

Alkaloids and Colon Cancer: Molecular Mechanisms and Therapeutic Implications for Cell Cycle Arrest

Cancer is the second most fatal disease worldwide, with colon cancer being the third most prevalent and fatal form of cancer in several Western countries. The risk of acquisition of resistance to chemotherapy remains a significant hurdle in the management of various types of cancer, especially colon cancer. Therefore, it is essential to develop alternative treatment modalities. Naturally occurring alkaloids have been shown to regulate various mechanistic pathways linked to cell proliferation, cell cycle, and metastasis. This review aims to shed light on the potential of alkaloids as anti-colon-cancer chemotherapy agents that can modulate or arrest the cell cycle. Preclinical investigated alkaloids have shown anti-colon cancer activities and inhibition of cancer cell proliferation via cell cycle arrest at different stages, suggesting that alkaloids may have the potential to act as anticancer molecules.     

Structure activity relationship studies on antileishmanial steroidal alkaloids from Sarcococca hookeriana

The search for antileishmanial constituents from the medicinal plant Sarcococca hookeriana (Buxaceae) of Nepalese origin has resulted in the isolation of 17 (1-17) active steroidal alkaloids. Compounds 1, 2, and 10 were subjected to derivatization and five chemically derived derivatives (1a, 2a, 10a, 10b, 10c) were also obtained. All these natural compounds and derivatives were found to have potent to mild antileishmanial properties. The IC(50) values were found to be in the range of 0.20-61.44 microg mL(-1) (IC(50) value of standard drug amphotericin B = 0.12 microg mL(-1)). The structure activity relationship indicated that the varieties of functionalities present in ring A of the steroidal alkaloids were found to play a characteristic role to increase the antileishmanial activity.     

Cross-coupling reactions towards the synthesis of natural products

Molecular Diversity - Cross-coupling reactions are powerful synthetic tools for the formation of remarkable building blocks of many naturally occurring molecules, polymers and biologically active...     

Travelling wave solutions and regularity results for nonlinear Newton-Schrödinger systems especially in one dimensions

Optical and Quantum Electronics - In the current paper, we try to engineer the refractive index profile in a one-dimensional photonic crystal as a powerful tool to manage the electromagnetic wave...     

Form Factor and rms Radius of Proton Predicted Using Differential Cross-Section Data of $${p\bar{p}}$$ Elastic Scattering at $${\sqrt{s}=31}$$ , 53, 62 and 1960 GeV

Physics of Atomic Nuclei - Using differential cross-section data on $$p\bar{p}$$ elastic scattering at $$\sqrt{s}=31$$ , 53, 62, and 1960 GeV, for low momentum transfer square (...     

Ultrasound Assisted Synthesis and In Silico Modelling of 1,2,4-Triazole Coupled Acetamide Derivatives of 2-(4-Isobutyl phenyl)propanoic acid as Potential Anticancer Agents

The development of an economical method for the synthesis of biologically active compounds was the major goal of this research. In the present study, we have reported the ultrasound-radiation-assisted synthesis of a series of novel N-substituted 1,2,4-triazole-2-thiol derivatives. The target compounds 6a–f were efficiently synthesized in significant yields (75–89%) by coupling 1,2,4-triazole of 2-(4-isobutylphenyl) propanoic acid 1 with different electrophiles using ultrasound radiation under different temperatures. The sonication process accelerated the rate of the reaction as well as yielded all derivatives compared to conventional methods. All derivatives were confirmed by spectroscopic (FTIR, ¹HNMR, ¹³CNMR, HRMS) and physiochemical methods. All derivatives were further screened for their anticancer effects against the HepG2 cell line. Compound 6d containing two electron-donating methyl moieties demonstrated the most significant anti-proliferative activity with an IC₅₀ value of 13.004 µg/mL, while compound 6e showed the lowest potency with an IC₅₀ value of 28.399 µg/mL. The order of anticancer activity was found to be: 6d > 6b > 6f > 6a > 6c > 6e, respectively. The in silico modelling of all derivatives was performed against five different protein targets and the results were consistent with the biological activities. Ligand 6d showed the best binding affinity with the Protein Kinase B (Akt) pocket with the lowest ∆G value of −176.152 kcal/mol. Compound 6d has been identified as a promising candidate for treatment of liver cancer.     

UV-absorption studies of interaction of karanjin and karanjachromene with ds. DNA: Evaluation of binding and antioxidant activity

Two flavonoids, karanjin (Kj) and karanjachromene (Kc) have been investigated spectrophotometrically for their mode of interactions with double stranded (ds)-DNA at blood (7.4) and stomach (4.7) pH and at human body temperature (37°C). Benesi-Hildebrand equation was used to evaluate the binding constants, K _b . Binding constants at both pH values and at body temperature showed stronger binding of both the flavonoids and formation of 1:1 flavonoid-DNA complex via intercalative mode. However, K _b values for karanjin were evaluated to be comparatively greater than karanjachromene at both pH values. The highest value of binding constant (1.32×10⁵ M^?1) for karanjin at blood pH (7.4) demonstrated its comparatively stronger binding and greater effectiveness at this pH. Standard Gibbs free energy changes (ΔG) of flavonoid-DNA complexes were calculated as negative values and indicative of spontaneity of their binding. Both flavonoids showed significant DNA protection activity.      

In vitro Toxicological Study of Metal Oxides Nanoparticles on Oxidation of Succinate in Krebs Cycle and Their Resultant Effect in Metabolic Pathways

In vitro study to evaluate toxic effects of metal oxides nanoparticles on energy producing cycle was conducted. In this study oxidation of sodium succinate in aqueous solution was investigated by using potassium ferricyanide as an oxidizing agent. Kinetic measurements were carried out on kinetic mode of spectrophotometer at λ_max 420 nm. Effect of different metal oxides (MgO and CaO) nanoparticles was observed on the oxidation of succinate at 25 ± 0.5 °C. These metal oxides nanoparticles were prepared by hydrothermal method and their characterization were done by using FTIR, TGA, SEM‐EDX, TEM and XRD. Kinetic results indicated that these nanoparticles inhibit the conversion of succinate into fumerate. The inhibition is directly dependent on particle size of the nanoparticles and it was observed that particle size is inversely related to the oxidation rate of succinate. It was concluded at the end that elevated concentrations of metal oxides nanoparticles can severely affect the Krebs cycle by inhibiting succinate oxidation and lead to various metabolic disorders.